RAB-10 Promotes EHBP-1 Bridging of Filamentous Actin and Tubular Recycling Endosomes

PLoS Genet. 2016 Jun 6;12(6):e1006093. doi: 10.1371/journal.pgen.1006093. eCollection 2016 Jun.

Abstract

EHBP-1 (Ehbp1) is a conserved regulator of endocytic recycling, acting as an effector of small GTPases including RAB-10 (Rab10). Here we present evidence that EHBP-1 associates with tubular endosomal phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] enriched membranes through an N-terminal C2-like (NT-C2) domain, and define residues within the NT-C2 domain that mediate membrane interaction. Furthermore, our results indicate that the EHBP-1 central calponin homology (CH) domain binds to actin microfilaments in a reaction that is stimulated by RAB-10(GTP). Loss of any aspect of this RAB-10/EHBP-1 system in the C. elegans intestinal epithelium leads to retention of basolateral recycling cargo in endosomes that have lost their normal tubular endosomal network (TEN) organization. We propose a mechanism whereby RAB-10 promotes the ability of endosome-bound EHBP-1 to also bind to the actin cytoskeleton, thereby promoting endosomal tubulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism*
  • Animals
  • Biological Transport / physiology
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism*
  • Endocytosis / physiology
  • Endosomes / metabolism*
  • Intestinal Mucosa / metabolism
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Protein Binding / physiology
  • Protein Transport / physiology
  • Vesicular Transport Proteins / metabolism*
  • rab GTP-Binding Proteins / metabolism*

Substances

  • Actins
  • Caenorhabditis elegans Proteins
  • EHBP-1 protein, C elegans
  • Phosphatidylinositol 4,5-Diphosphate
  • Vesicular Transport Proteins
  • RAB-10 protein, C elegans
  • rab GTP-Binding Proteins